tbuckley/cabot-search huggingface dataset:
Facility-level disparities in the delivery of guideline-based treatment across genitourinary cancers.
Authors: Julie A. Szymaniak, Li Zhang, Sima P. Porten, Maxwell Meng, Matthew R. Cooperberg, Peter Carroll, Samuel L. Washington
Journal: Journal of Clinical Oncology (2023)

456 Background: Disparities in guideline-based treatment (GBT) for genitourinary cancers are commonly presented individually, impeding comprehensive examinations of institutional drivers. While patient-level factors impacting disparities in treatment have been well documented, our understanding of how race-based disparities in treatment exist at the institution level remains relatively limited. In this study, we aim to characterize the prevalence of disparities in GBT for prostate (PCa), bladder (BCa), and kidney (KCa) cancer within the same facility to evaluate whether disparities cluster at the institutional level. Methods: Patients diagnosed with clinically localized (cT2-4aNX-1MX-0) bladder, (cT2b-4NX-0MX-0) prostate, or (cT2a-3cNX-1MX-0) kidney cancer between 2004-2017 within each National Cancer Database dataset were included. We collected clinicodemographics, treatment received, and facility data. GBT was defined according to NCCN Guidelines by TNM staging. We calculated rates of GBT by cancer type and race and compared rates between White, Black, Hispanic, and Asian patients using Chi-squared tests. Pairwise correlations in GBT rates between PCa, BCa, and KCa treated across and within facilities were estimated using Pearson correlation coefficients, where facilities with &lt;10 cases of each cancer were excluded. Results: We identified 91904 BCa, 73,050 KCa, and 252,403 PCa cases. Overall, unadjusted GBT rates for BCa (41%, SD 18%) were significantly lower than for KCa (72%, SD 17%) and PCa (77%, SD 16%), all p&lt;0.001. Correlation coefficients at academic medical centers were highest among the four facility types, though still low (r=0.31 prostate-bladder, 0.39 prostate-kidney, 0.39 bladder-kidney). BCa GBT was highest for White and Asian patients (50.5% and 48.6%, respectively) versus 42.2% for Black patients. KCa GBT rates were equivalent for White, Hispanic, and Asian patients (~76%) but lowest for Black patients (74.8%). In PCa, the highest GBT rate was 80.8% (White patients) and lowest was 76.5% (Black patients). After controlling for confounding variables and matching based on cohort size, intra-facility odds of receipt of GBT by Black patients (compared to White counterparts) correlated poorly across cancer types for all comparisons. This was true even when restricting analysis to higher-volume facilities (&gt;200 patients), with r=0.1 for bladder-kidney, 0 for bladder-prostate, and 0.12 for kidney-prostate; p-value &gt;0.05. Conclusions: Our findings show that, overall, there is little correlation between racial disparities in GBT across GU cancers treated in the same facility. As we push further for interventions to combat racial inequities in healthcare, we must continue to explore their prevalence within the context of a multi-disease and multi-level paradigm to identify systems-level factors that perpetuate their existence.
Safety, tolerability, and preliminary efficacy of TAR-200 in patients with intermediate risk non–muscle-invasive bladder cancer: A phase 1 study.
Authors: F. Johannes P. van Valenberg, Toine van der Heijden, Christopher Cutie, Sumeet Kaur Bhanvadia, Kirk A. Keegan, Shalaka Hampras, Hussein Sweiti, John Maffeo, Shu Jin, Albert Chau, Don Reynolds, Crysti Iarossi, April Kelley, Xiang Li, Katherine Stromberg, Michiel Sedelaar, Jessica Steenbruggen, Diederik Meindert Somford, Alfred Alfred Witjes
Journal: Journal of Clinical Oncology (2023)

505 Background: TAR-200 is a novel intravesical drug delivery system designed to provide a continuous, slow release of gemcitabine within the bladder. Prolonged gemcitabine exposure over days, instead of hours, such as with current standard intravesical installations, may achieve more efficient and effective tumor response. We report on the safety and tolerability of TAR-200 in patients with non-muscle–invasive bladder cancer (NMIBC). Methods: In this phase 1b, open-label, prospective study, patients with a papillary recurrence after prior histologically proven, intermediate risk (IR)-NMIBC received two 1-week TAR-200 dosing cycles over a 4- to 6-week period. The study used a marker lesion/ablation design. Cystoscopy was performed to assess for recurrent papillary disease and for complete transurethral resection of the residual bladder tumor. The primary outcome was safety of TAR-200. Secondary outcomes were tolerability, pharmacokinetics, preliminary efficacy, and immunohistochemistry. Results: In total, 12 patients received TAR-200 treatment. Insertion and removal of TAR-200 was uneventful. No TAR-200-related serious adverse events (AEs) occurred. Four patients had no TAR-200-associated AEs; the remainder had varying degrees of AEs (all grade ≤2 [CTCAEv4.0]), mainly consisting of low-grade urinary urgency, urinary frequency, and dysuria, with no delay in the treatment schedule. Two patients refused a second dosing cycle due to urinary urgency and frequency. Plasma gemcitabine concentrations remained below the lower limit of detection. Five of 12 patients (42%) had complete response (CR); of these, 4 had a pathologic CR and 1 had CR based on visual assessment (with no biopsy available for pathologic assessment). Conclusions: In this small, phase 1 series, TAR-200 appears to be safe and well tolerated in patients with IR-NMIBC. Clinical trial information: NCT02720367 .
Baseline characteristics from a retrospective, observational, US-based, multicenter, real-world (RW) study of avelumab first-line maintenance (1LM) in locally advanced/metastatic urothelial carcinoma (la/mUC) (PATRIOT-II).
Authors: Petros Grivas, Pedro C. Barata, Helen Moon, Thomas E. Hutson, Shilpa Gupta, Cora N. Sternberg, Vaidehi Dave, Chad Downey, Alicia C. Shillington, Geeta Devgan, Melissa Kirker, Sheena Thakkar, Howard M. Katzenstein, Abhijeet Bhanegaonkar, Frank Liu, Jason Brown, Guru P. Sonpavde
Journal: Journal of Clinical Oncology (2023)

465 Background: The JAVELIN Bladder 100 clinical trial demonstrated a significant overall survival and progression-free survival benefit with avelumab 1LM + best supportive care (BSC) vs BSC alone for la/mUC not progressing on platinum-based chemotherapy (PBC). PATRIOT-II aims to describe RW data for avelumab 1LM treatment (tx) of patients (pts) with la/mUC. Methods: PATRIOT-II collected data from pts with la/mUC treated in 37 geographically dispersed oncology practices/communities and academic centers in the US. Pts who initiated avelumab 1LM following PBC were retrospectively enrolled and will be followed up via medical record review for 52 weeks post avelumab 1LM initiation. This analysis focused on pt characteristics and tx data from la/mUC diagnosis through the PBC period and at avelumab 1LM initiation. Disease and PBC tx characteristics, as well as response to PBC, were assessed. All analyses were descriptive. Results: A total of 160 pts were enrolled (Table), 118 (74%) were white, non-Hispanic, 16 (10%), were Black, Asian, or Hispanic, and the rest unknown; 102 (64%) were current or former smokers. 77 (48%) were tested for PD-L1 via various assays, with 44 (57%) of those tumor samples reported as positive. 1L PBC was cisplatin-based in 100 (63%) of pts and carboplatin-based in 60 (38%). Pts received a median of 4 PBC cycles (interquartile range [IQR], 3-6) for a median of 13 weeks (IQR, 10-17). 31 (19%) discontinued PBC due to unacceptable side effects/toxicity. Best observed response was complete response in 21 (13%), partial response in 109 (68%), and stable disease in 17 (11%), with the remainder unknown. Median time to first imaging was 10 weeks (IQR, 5-14) after PBC initiation. 23 (14%) were hospitalized while receiving PBC, and 25 (16%) were seen in the emergency department. Pts proceeded to avelumab 1LM at a median of 4 weeks (IQR, 3-6) following PBC completion. Avelumab was administered at 800 mg every 2 weeks in 130 (81%), 10 mg/kg in 15 (9%), &lt;800 mg in 8 (5%), and &gt;800 mg in 7 (4%) pts. Conclusions: This ‘RW’ study offers valuable insights into characteristics and outcomes of pts with la/mUC treated in the US. Baseline factors, tx patterns and response to PBC were consistent with usual therapy paradigms in the 1L induction setting. Ongoing trials are evaluating the optimal number of PBC cycles and predictive biomarkers. Limitations include the retrospective nature, lack of randomization and central review, potential selection and confounding biases. [Table: see text]
Leptomeningeal metastases in prostate cancer: A systematic review.
Authors: Sharon In Wha Choe, Jue Wang
Journal: Journal of Clinical Oncology (2023)

53 Background: Leptomeningeal metastasis (LM) is a rare complication of prostate cancer (PCa) that involves spread of malignant disease to the meninges and carries a poor prognosis. This review aimed to assess the clinical findings, treatments, and outcomes of LM cases reported in the literature. Methods: We performed a literature search for case reports in PubMed, Scopus, and ScienceDirect from database inception to June 2022 using keywords “leptomeningeal carcinomatosis AND prostate cancer” and “leptomeningeal metastases AND prostate cancer.” The reference lists of previously published reviews were also searched to identify additional articles. Results: We included 41 patients with a mean age (±SD, range) at diagnosis of 67.5 (8.4, 46-87) years. The most common presenting symptoms were headache (32%), leg weakness (24%), nausea (22%), vomiting (20%), vision complaints (17%), sensory abnormalities (17%), back pain (12%), and confusion (12%). The median time from initial PCa to LM diagnosis was 36 months (range 0-252) and was reported in 37 patients (90%). The median time of survival from LM to death was 1.7 months (range 4 days – 14 months) and was reported in 28 patients (68%). Four patients (13%) were still alive when the reports were written, including one who was alive at 16 months and another at 252 months. The median serum PSA (±SD, range) at time of diagnosis was 137.5 (507.9, 3.1-1500) ng/mL. The most common diagnostic tests were a combination of neuroimaging and CSF analysis (41%), neuroimaging only (32%), and autopsy only (12%). The most common imaging modalities used to aid diagnosis were MRI (65%) and CT (32%). CSF cytology was positive for malignant cells in 55% of 22 cases (54%) that reported cytology results. Thirty-four cases (83%) reported treatments, and the most common treatments were radiation (56%), steroids (32%), surgery (26%), hormonal therapy (21%), and chemotherapy (21%). Conclusions: LM is expected to become more prevalent with the overall increasing incidence of PCa with therapeutic advancements, yet it remains difficult to diagnose and treat. The findings of this review suggest that neurological symptoms in patients with advanced PCa should prompt providers to obtain neuroimaging to investigate possible LM.
Geographic variation of decipher genomic classifier in patients with early prostate cancer.
Authors: Daniel Keizman, Elai Davicioni, Avivit Peer, Hadas Dresler, Avishay Sella, David Leonid Sarid, Keren Rouvinov, Yoav Manaster
Journal: Journal of Clinical Oncology (2023)

376 Background: External factors such as environmental or lifestyle-related exposure may influence genomic composition of cancer, and therefore its progression and outcome. Thus geographic data is of importance. Decipher is a gene expression classifier used in risk stratification of early non metastatic prostate cancer. Currently, there are no data reporting geographic variation of the test. We aimed to analyze Decipher genomic score results among Israeli patients, in comparison to American patients. Methods: The Decioher database (Decipher Biosciences Inc) contains data from patients who have given consent for broad data-sharing. We identified and analyzed Decipher test results ordered among Israeli patients with localized prostate cancer. Matched analysis to the US population was done. Results: 144 patients (median age 69.5, range 64-74) were included in the present analysis. The clinical NCCN risk grouping was low in 42.4% (n=61), favorable intermediate in 38.9% (n=56), unfavorable intermediate in 17.4% (n=25), and high risk in 1.4% (n=2). Physicians primarily obtained Decipher for low-intermediate NCCN risk. Median Decipher score was 0.57 (Q1 0.385, Q3 0.823). Decipher risk grouping was low in 38.1% (n=61), intermediate in 16.9% (n=27), and high in 45% (n=72). Median Decipher score increased with Grade Group. 46% of NCCN low risk patients had a higher risk as per Decipher. 82% of NCCN favorable intermediate and unfavorable intermediate risk were reclassified to lower or higher risk. 9% of NCCN high risk patients had a lower risk as per Decipher. The present study cohort had a higher proportion of higher Decipher scores than observed in similar grade US population (n=43065) in the Decipher database (Median 0.43, Q1 0.27, Q3 0.66; 52%/18%/30% with low/intermediate/high risk). Conclusions: The preliminary results of the present study suggest a higher proportion of high risk Decipher among Israeli patients with early prostate cancer. These results should be interpreted cautiously. The study and further data collection are ongoing.
Extracellular domain<i> ERBB2 </i>(<i>ERBB2</i> ECD+) mutations in urothelial bladder cancer (UBC).
Authors: Michael Basin, Joseph M Jacob, Gennady Bratslavsky, Petros Grivas, Philippe E. Spiess, Roger Li, Andrea Necchi, Dean C. Pavlick, Richard S.P. Huang, Douglas I. Lin, Natalie Danziger, Ethan Sokol, Smruthy Sivakumar, Jeffrey S. Ross
Journal: Journal of Clinical Oncology (2023)

566 Background: Given the recent approval in lung cancer for the first anti-HER2 targeted therapy directed against activating kinase domain exon 20 ERBB2 insertion mutations, considerable interest has arisen in targeting additional locations in the ERBB2 gene in other tumor types. Methods: 5,485 UBC samples were sequenced using a hybrid capture-based comprehensive genomic profiling (CGP) assay to assess all classes of genomic alterations (GA), tumor mutational burden (TMB), microsatellite instability (MSI), genomic loss of heterozygosity (gLOH), trinucleotide signatures and predominant genetic ancestry. Statistical comparisons utilized the Bonferroni correction. Results: 548 (10.0%) of UBC featured ERBB2 gene amplification (amp) and 219 (4.0%) featured an ERBB2 ECD+ sequence mutation (74% S310F and 26% S310Y). ERBB2 ECD+ mutations and ERBB2 amplification were mutually exclusive. 16.4% of ERBB2 ECD+ UBC had more than one E RBB2 sequence mutation. Central pathology review of the 219 ERBB2 ECD+ UBC revealed that 63 (28.8%) featured a micropapillary histologic appearance (MPUC). ERBB2 ECD+ UBC featured more patients with European ancestry than both ERBB2 WT (90.9% vs 84.2%; p=.03) and ERBB2 amp (90.9% vs 83.2%; p=.04). ECD mut+ UBC also featured lower association with African ancestry than ERBB2 amp (2.7% vs 7.8%; p=.04) and lower frequency of gLOH &gt; 16% (9.3% vs 19.1%; p=.04). MSI-High status was similar and rare in all 3 groups (range 0 to 0.9%). ERBB2 ECD+ UBC had a higher frequency of APOBEC signature than ERBB2 amp (82.9% vs 72.4%; p=.03). TMB &gt; 10 mut/mb was higher in ERBB2 amp (49.2% vs 31.4%; p&lt;.0001) and ERBB2 ECD+ (59.8% vs 31.4%; p&lt;.0001) compared to ERBB2 WT as was the mean TMB (11.8 and 17.4 mut/Mb respectively vs 8.9 mut/Mb, p&lt;0.001 for both). Among important UBC individual genes, FGFR3 GA were significantly higher in ERBB2 WT than both ERBB2 amp (19.9% vs 6.2%; p&lt;.0001) and ERBB2 ECD+ (19.9% vs 10.5%; p=.0002). CDKN2A GA were significantly higher in ERBB2 amp (39.1% vs 27.9% ERBB2 WT; p&lt;.0001) only. The higher frequency of KMT2D GA in MPUC+ ECD+ and MPUC- ECD+ UBC (63.4% vs 27.6%; p=.02) was the only genomic difference between these cohorts. Conclusions: ERBB2 ECD mutation driven UBC is a unique form of UBC featuring enrichment of MPUC histology and a unique clinical and genomic landscape including genomic signatures and ancestry.
Clinical utility of IDC-P (intraductal carcinoma of the prostate) in the decision making of initial treatment for metastatic hormone-sensitive prostate cancer.
Authors: Yushi Naito, Masashi Kato, Akiyuki Yamamoto, Toyonori Tsuzuki
Journal: Journal of Clinical Oncology (2023)

93 Background: In recent years, the usefulness of using androgen receptor axis-targeted agents (ARAT) such as abiraterone, enzalutamide, and apalutamide for metastatic hormone-sensitive prostate cancer (mHSPC) in the up-front setting has been demonstrated. However, it is still unclear which patients could truly benefit from these treatments. On the other hand, intraductal carcinoma of prostate (IDC-P) is a known poor prognostic factor for prostate cancer patients. In the present study, we investigated the association between the presence of IDC-P and therapeutic response to mHSPC. Methods: This retrospective analysis included 318 patients with mHSPC from thirteen affiliated institutions between 2014 and 2021, and evaluated biopsy specimens for the presence of IDC-P. All patients were grouped by their first-line treatment, either ARAT (n=100, receiving a combination of androgen-deprivation therapy [ADT] and ARAT), or conventional therapy (n=218, receiving ADT with or without standard antiandrogen agents). We compared overall survival (OS) and second progression-free survival (PFS2) between the ARAT and conventional groups according to the presence of IDC-P to evaluate whether presence of IDC-P predicts response to each treatment. The PFS2 was defined as the period from diagnosis of mHSPC to disease progression on second-line therapy or death. Propensity score matching was used for one-to-one nearest neighbor matching in order to minimize the potential effects of selection bias and confounding factors. The clinicopathological variables of patients were well balanced after propensity score matching. Results: Most patients in the ARAT (79%) and conventional therapy (71%) groups were ICD-P positive. In the propensity score-matched cohort, OS and PFS2 of IDC-P positive cases were significantly prolonged in the ARAT group compared to the conventional group (OS: hazard ratio [HR], 0.36; p=0.047; PFS2: HR, 0.30; p&lt;0.001). In contrast, IDC-P negative cases did not show a difference in OS and PFS2 between the ARAT and the conventional groups (OS: HR, 1.09; p=0.920; PFS2: HR, 0.40; p=0.264). Conclusions: The findings highlight a high prevalence of IDC-P among patients with mHSPC and suggest that IDC-P may be a reliable indicator to implement ARAT as first-line therapy.
A retrospective review of primary prophylaxis with granulocyte-colony stimulating factor (G-CSF) for patients with genitourinary malignancies receiving chemotherapy during the COVID-19 pandemic and implications for the future.
Authors: Nely Mercy Diaz Mejia, Carlos Stecca, Di Maria Jiang, Nazanin Fallah-Rad, Philippe L. Bedard, Vikaash Kumar, Osama Abdeljalil, Amer Zahralliyali, Husam Alqaisi, Esmail Mutahar Al-Ezzi, Vivian Choy, Parmvir Banwait, Eshetu Atenafu, Srikala S. Sridhar
Journal: Journal of Clinical Oncology (2023)

115 Background: To mitigate the risks of chemotherapy associated neutropenia, during the COVID-19 pandemic, all genitourinary (GU) cancer patients treated with chemotherapy at the Princess Margaret Cancer Centre (PMCC) were offered primary prophylaxis with GCSF. We hypothesize that this reduced rates of febrile neutropenia, hospitalizations, healthcare costs and improved overall outcomes, compared to GU cancer patients treated with chemotherapy without GCSF in the 2 years prior to the pandemic. Methods: We performed a retrospective review of GU cancer patients, receiving curative or palliative intent chemotherapy, with or without primary GCSF prophylaxis between January 2018 and June 2022. GCSF was given either as a single dose or as consecutive doses post chemotherapy. Main outcomes were incidence of febrile neutropenia, hospitalization, health care expenditures as well as disease specific outcomes. Results: Overall, 248 patients with prostate cancer (44%), urothelial cancers (33%) germ cell (21%), and rare GU cancers (4%) were identified. Median age was 70 (range 19-91), 92% were male, 65% were ECOG 0/1. Treatment intent was neoadjuvant (13%), adjuvant (20%), or palliative (67%). Main regimens used were docetaxel, cabazitaxel, carboplatin, cisplatin/etoposide, gemcitabine/cisplatin and BEP. Median follow-up was 10.5 months (0.23-52.3 months). A total of 206/248 received primary GCSF prophylaxis. During chemotherapy, the median white blood cell levels were higher in the GCSF group compared to the non-GCSF group (14.1*10*9/L vs 2.90*10*9/L, p&lt;0.0001); and neutropenia rates were markedly lower (2% vs. 93%, P=&lt;0.0001). Hospital admission rates were significantly lower in G-CSF users compared to non-users (19% vs. 69%, P&lt;0.0001). Symptomatic disease progression 13% was the leading cause of admission in the G-CSF group. Infectious causes such as UTI, pneumonia, COVID-19, and sepsis were seen in only 12% of the G-CSF group compared to 31% in the non-users. G-CSF was generally well tolerated with just 0.97% discontinuing G-CSF. Conclusions: During the COVID-19 pandemic, primary prophylactic G-CSF use in GU cancer patients, undergoing chemotherapy significantly lowered rates of both febrile neutropenia and hospitalizations and could be a cost-effective strategy in this patient population that warrants further study.
Renal function and survival following treatment for cT1N0 renal cell carcinoma in a veteran population.
Authors: Abhishek Kumar, Joseph Kamel Salama, Matthew J Boyer
Journal: Journal of Clinical Oncology (2023)

642 Background: Radical nephrectomy (RN), nephron sparing surgery (NSS) and thermal ablation (TA) are associated with similar oncologic control for early-stage renal cell carcinoma (RCC). However, the potential protective role of nephron sparing treatments on renal function and its impact on non-cancer related mortality remains undetermined. Methods: We employed the national Veterans Affairs Corporate Data Warehouse (CDW) to identify patients diagnosed with cT1N0 RCC between 2000-2018. Laboratory and diagnosis data were used to calculate creatinine clearance and Charlson comorbidity score. Chronic kidney disease (CKD) was defined as creatinine clearance &lt; 60 milliliters per minute. Kaplan-Meier analysis and multivariable Cox regression analysis were used to evaluate overall survival. Results: Overall, there were 8279 Veterans with cT1N0M0 renal cell carcinoma diagnosed between 2000-2018 who received either RN (2946, 36%), NSS (4846, 59%) or TA (487, 6%). Median follow up time was 8 years (90% CI 2-15 years). Patients receiving RN were older than those receiving NSS (median age 64.0 vs 62.6 years, p&lt;0.01) but younger than those receiving TA (median age 67.9 years, p&lt;0.01). Patients receiving RN and TA had more comorbidities than patients receiving NSS (mean Charlson scores 0.76 vs. 1.00 vs. 0.66, p&lt;0.01. More patients among the RN group had CKD before RCC diagnosis than the NSS and TA groups (10% vs. 6% vs. 7%, p&lt;0.01). Among the subset of patients without CKD before treatment, 17% of RN, 8% of NSS, and 11% of TA developed CKD at least 1 year after treatment, (p &lt;0.01). Median OS was 11.5 years with RN, 14.2 years with NSS, and 10.3 years with TA. On multivariable analysis considering age, comorbidities, CKD, race, and year of treatment, compared to RN, NSS was associated with better OS (HR 0.75, p&lt;0.01) with a trend to improved survival with TA (HR 0.88, p=0.08). Conclusions: NSS or TA are associated with less post-operative renal dysfunction than RN in patients treated for cT1N0 RCC in the VAHCS. NSS is associated with improved OS compared to RN. Further studies are warranted to assess the impact of renal dysfunction in this population in relation to oncologic and survival outcomes.